B. Abstract Damage to peripheral nerves as a result of trauma is a frequent event that incapacitates hundreds of thousands of people in the US and around the world. Despite a long history of research into the mechanisms of peripheral nerve injury and regeneration, outcomes of nerve repair are still unsatisfactory especially in patients with complete transection of mixed nerves at proximal locations. Likely reasons for poor recovery after peripheral nerve injury in these cases are that feedback signals from regenerated afferents in self-reinnen/ated muscles do not elicit reflex responses in the motoneurons (loss of proprioceptive input to the central nervous system) and that activity of proximal two-joint muscles is heavily dependent on proprioceptive feedback. The goal of this proposal is to develop a basis for novel therapeutic interventions to improve functional recovery after nerve injury by investigating the sensory control of proximal two-joint muscles. In Aim 1, we will determine the effects of lost proprioceptive input after self-reinnervation of cat proximal one-joint and two-joint muscles on whole body locomotion. We will test specific predictions about locomotor changes in activity of multiple hindlimb muscles and whole-body mechanics resulting from reinnervation of quadriceps and different heads of the biceps femoris muscles. In Aim 2, we will investigate sensory mechanisms of functionally appropriate motor compensations that occur after denegeration of selected hindlimb muscles. By sequentially reinnervating all major synergists at a joint, we will determine the extent to which proprioceptive input from selected intact synergists contributes to functionally appropriate compensatory responses to muscle denervation. In Aim 3, we will determine the effects of varying onset times of locomotor training on recovery of locomotor patterns and reflex responses of self-reinnervated proximal hindlimb muscles. The studied therapeutic interventions will include locomotor conditions with increased demands on proprioceptive input or mechanical output from the affected muscles.